Chlorin E6 Research Articles

A nano drug delivery system loading drugs and chlorin e6 separately to achieve photodynamic-chemo combination therapy.

To develop a new drug delivery system (DDS) that can load chemotherapy agents and photosensitizer chlorin e6 (Ce6) onto the pores and surfaces of mesoporous silica nanoparticle (MSN) separately. Doxorubicin (DOX) was loaded into the pores of MSNs. Then, polyethyleneimine (PEI) was used to coat the surface of MSN to protect DOX, and then manganese dioxide (MnO2) nanoparticles were loaded through adding potassium permanganate (KMnO4) to bind with Ce6. Finally, polydopamine (PDA) was coated and coupled with hyaluronic acid (HA). The synthesized versatile nanoparticle was pH-sensitive and exhibited positive photodynamic therapy (PDT) performance. Besides, it could be observed that the nanoparticles were efficiently taken up by tumor cells through confocal laser scanning microscopy (CLSM) and flow cytometry. Additionally, in vitro experiments suggested that the nanoparticles had pleasing toxicity to various tumor cells and equally positive therapeutic effect when curcumin replaced DOX. Our work suggests that the nanoparticles designed by our strategy have satisfactory combination therapy performance and can enable more chemotherapy drugs to be used in photodynamic-chemo combination therapy.

Bidirectional Amplification of Oxidative Stress via Mitochondria-Targeted Co-Delivery of Nanogolds and Chlorin e6 Using ROS-Responsive Organosilica Nanocarriers.

Bidirectional amplification of oxidative stress within the mitochondria is essential to enhance photodynamic therapy (PDT), and efficient co-delivery of reducing agents and reactive oxygen species (ROS)-generating agents is critical for achieving this with minimal side effects. However, the absence of an effective platform for mitochondria-targeted co-delivery and spatially controlled tumor-specific therapy limits the potential applicability of this strategy. In this study, we developed an ROS-sensitive organosilica nanocarrier, encapsulating nanogold and introducing chlorin e6 (Ce6) and triphenylphosphine (TPP) through a one-pot sol-gel process. Following TPP-mediated mitochondria-targeted delivery, ROS generated by Ce6 under near-infrared (NIR) irradiation not only damaged the mitochondria but also disrupted the nanoparticles within the tumor, leading to the release of nanogold. These ultra-small nanogolds, due to their high surface area, exhibited enhanced glutathione scavenging capacity, which, in combination with ROS, synergistically amplified oxidative stress to overcome the high resistance of tumor cells. Both in vitro and in vivo experiments confirmed the effectiveness of this strategy, demonstrating efficient co-delivery, controlled drug release, spatially targeted oxidative stress amplification, and synergistic antitumor effects. Thus, we present a facile platform for the spatially controlled bidirectional amplification of oxidative stress with minimal side effects. STATEMENT OF SIGNIFICANCE: Mitochondrial oxidative stress involves both ROS generation and GSH depletion, indicating that bidirectional amplification is required for mitochondria-targeted antitumor therapy. However, most of existing strategies just focus on ROS generation, which limits the amplification level of oxidative stress. Thus, the mitochondria-targeted co-delivery of photodynamic agent and GSH scavenging agent is an effective approach to address this limitation. Besides, the lack of facile nanoplatform also hinders the application of strategies aimed at bidirectionally amplifying oxidative stress. In this study, we developed a facile nanoplatform for mitochondria-targeted co-delivery of the photodynamic agent Chlorin e6 and GSH scavenging agent nanogold using a ROS-responsive organosilica nanocarrier. This approach successfully achieved bidirectional amplification of oxidative stress, resulting in a synergistic antitumor effect with minimal side effects.

Light-activated photosensitizer/quercetin co-loaded extracellular vesicles for precise oral squamous cell carcinoma therapy.

Oral squamous cell carcinoma (OSCC) is the most common subtype of head and neck malignancies, characterized by a five-year survival rate that remains persistently below 50%, indicative of limited progress in therapeutic interventions. There is an urgent imperative to develop innovative therapeutic strategies, warranting the investigation of advanced treatment modalities. Nanocarriers offer a promising avenue by significantly enhancing drug properties and pharmacokinetics. Extracellular vesicles (EVs) are naturally occurring nanocarriers produced by cells and have become a focal point in drug delivery research. Quercetin, one of the most abundant dietary flavonoids, exhibits potent anticancer effects. However, its pharmaceutical application is hampered by poor water solubility, instability under physiological conditions, and low bioavailability. To overcome these obstacles, we propose using bio-derived EVs as carriers to co-encapsulate quercetin with the photosensitizer chlorin e6. This strategy leverages the intrinsic targeting capabilities of EVs for precise drug delivery to tumors, along with light-activated drug release, enabling rapid quercetin release under near-infrared light, effectively inhibiting cellular proliferation and inducing apoptosis in tumor cells. In vivo studies demonstrated that drug-loaded EVs exhibited robust tumor-targeting efficacy, resulting in effective and selective tumor ablation upon photoactivation in mice bearing subcutaneous MOC2 tumors.

Polymer-based nanodrugs enhance sonodynamic therapy through epigenetic reprogramming of the immunosuppressive tumor microenvironment.

While sonodynamic therapy (SDT) has shown promise in treating triple-negative breast cancer (TNBC) due to its non-invasive nature, deep tissue penetration, and induction of immunogenic cell death (ICD), its efficacy remains limited by the complex immunosuppressive tumor microenvironment (TME). In this study, we developed tumor microenvironment-responsive nanoparticles (GdNPs) to enhance SDT effectiveness through epigenetic reprogramming of the TME by encapsulating the sonosensitizer chlorin e6 (Ce6) and the histone deacetylase 6 (HDAC6) inhibitor Ricolinostat (Ric) (GdNPs/Ce6-Ric). GdNPs/Ce6-Ric effectively accumulate at tumor sites via the enhanced permeability and retention (EPR) effect and release Ce6 and Ric in response to the acidic TME. Upon ultrasound stimulation, GdNPs/Ce6-Ric induce cancer cell apoptosis and trigger ICD by generating reactive oxygen species (ROS), which activate cytotoxic T cells and promote tumor cell elimination. Notably, the epigenetic modulation by Ric within the immunosuppressive TME increased the proportion of natural killer (NK) cells and cytotoxic T cells while decreasing the population of immunosuppressive regulatory T (Treg) cells. This modulation synergistically enhanced the anti-tumor effects of SDT by downregulating the HDAC6/p-STAT3/PD-L1 pathway. Furthermore, GdNPs/Ce6-Ric minimized lung metastases by not only improving systemic immune responses but also inhibiting TGFβ-induced epithelial-mesenchymal transition (EMT) of tumor cells through the blockade of α-tubulin deacetylation. Thus, GdNPs/Ce6-Ric-based epigenetic modulation of the immunosuppressive TME offers a promising approach to enhance the efficacy of SDT in treating TNBC.

Chlorin e6: a promising photosensitizer of anti-tumor and anti-inflammatory effects in PDT.

Photodynamic therapy (PDT) involves the activation of photosensitizers (PSs) by visible laser light at the target site to catalyze the production of reactive oxygen species, resulting in tumor cell death and blood vessel closure. The efficacy of PDT depends on the PSs, the amount of oxygen, and the intensity of the excitation laser. PSs have been extensively researched, and great efforts have been made to develop an ideal photosensitizer. Chlorin-e6 is an FDA-approved second-generation PSs that has attracted widespread research interest in the medical field, especially with respect to antitumor and anti-inflammatory activity. Chlorin-e6 possesses the advantages of a large absorption coefficient, high strength, low residue in the body, and relatively high safety and thus has promising application prospects. Here we review the use of chlorin-e6 in PDT and discuss the prospects of further development of this technology.

Dual Pathways of Photorelease Carbon Monoxide via Photosensitization for Tumor Treatment.

Carbon monoxide (CO) gas therapy, as an emerging therapeutic strategy, is promising in tumor treatment. However, the development of a red or near-infrared light-driven efficient CO release strategy is still challenging due to the limited physicochemical characteristics of the photoactivated carbon monoxide-releasing molecules (photoCORMs). Here, we discovered a novel photorelease CO mechanism that involved dual pathways of CO release via photosensitization. Specifically, the photosensitizer Chlorin e6 (Ce6) sensitized oxygen to produce singlet oxygen (1O2) and oxidized photoCORM Mn2(CO)10 to release CO in an air-saturated solvent under red light (655 nm, 50 mW/cm2) irradiation. Furthermore, Ce6 and Mn2(CO)10 could undergo multistep photochemical reactions to release CO, as well as the degradation of the photosensitizer Ce6 in an oxygen-depleted solution. As a proof of concept, we demonstrated the feasibility and tumor inhibition of this CO release strategy both in vitro and in vivo. These results provide a robust platform for the development of new approaches to CO-mediated modulation of signaling pathways and further facilitate the practical use of gas therapeutic methods in tumor therapy in vivo.

Ex Vivo Biosafety and Efficacy Assessment of Advanced Chlorin e6 Nanoemulsions as a Drug Delivery System for Photodynamic Antitumoral Application

The photosensitizer (PS) in the Photodynamic Therapy (PDT) field represents a key factor, being directly connected to the therapeutic efficacy of the process. Chlorin e6 is a second-generation photosensitizer, approved by the FDA with the most desired clinical properties for PDT applications, presenting high reactive oxygen species (ROS) generation and proven anticancer properties. However, hydrophobicity is a major limitation, leading to poor biodistribution. To overcome this condition, the present work developed an up-to-date nanoemulsion incorporating Ce6 in a new nanosystem (Ce6/NE). A comprehensive study of physicochemical properties, stability, fluorescence characteristics, the in vitro release profile, in vivo and ex vivo biocompatibility, and ex vivo efficacy was established. The nanoemulsions showed the desired particle size and stability over six months, with no spectroscopic or photophysical alterations. Uptake studies demonstrated the internalization of the Ce6/NE in monolayers, with biocompatibility at the lowest concentrations. The HET-CAM assay, however, revealed a higher biocompatibility range, also indicating Ce6/NE’s potential for cancer treatment through antiangiogenic studies. These findings highlight the use of a new promising photosensitizer for PDT modulated with nanotechnology that promotes low toxicity, higher bioavailability, and site-specific delivery.

Photosensitive Hybrid γδ-T Exosomes for Targeted Cancer Photoimmunotherapy.

Melanoma is the most aggressive type of skin cancers. Traditional chemotherapy and radiotherapy have limited effectiveness and can lead to systemic side effects. Photodynamic therapy (PDT) is a photoresponsive cancer therapy based on photosensitizers to generate reactive oxygen species (ROS) to eradicate tumor cells. Our previous study showed that exosomes derived from human γδ-T cells (γδ-T exosomes) could control Epstein-Barr virus-associated tumors. Here, we combined γδ-T exosomes and PDT for targeted photoimmunotherapy by membrane fusion of γδ-T exosomes and Chlorin e6 (Ce6)-loaded liposomes. The functional surface proteins, such as CCR5 and PD-1, on the hybrid exosomes mediated the specific binding of hybrid exosomes toward melanoma tissues. The cytolytic molecules, such as granzyme A, granzyme B, perforin, and granulysin from γδ-T exosomes, induced specific apoptosis of cancer cells without harming normal cells. In response to light irradiation, ROS generation inside melanoma cells synergized with cytolytic molecules to induce apoptosis and promote immunogenic cancer cell death (ICD). The subsequently released damage-associated molecular patterns (DAMPs) could stimulate human dendritic cell maturation and induce melanoma antigen-specific CD4+ and CD8+ T-cell responses, thereby enhancing antitumor immunity. This study provides a promising strategy by combining γδ-T exosomes and PDT for photoimmunotherapy, thereby expanding the clinical applications of γδ-T exosome therapy for cancer patients.

Bioorthogonal reaction-mediated photosensitizer-peptide conjugate anchoring on cell membranes for enhanced photodynamic therapy.

Photodynamic therapy (PDT), utilizing a photosensitizer (PS) to induce tumor cell death, is an effective modality for cancer treatment. PS-peptide conjugates have recently demonstrated remarkable antitumor potential in preclinical trials. However, the limited cell membrane binding affinity and rapid systemic clearance have hindered their transition to clinical applications. To address these challenges, we investigated whether in vivo covalent chemistry could enhance tumor accumulation and potentiate antitumor efficacy. Specifically, we synthesized a PS-peptide conjugate termed P-DBCO-Ce6, with chlorin e6 (Ce6) and dibenzocyclooctyne (DBCO) conjugated to a negatively charged short peptide. By employing metabolic glycoengineering and bioorthogonal reactions, P-DBCO-Ce6 achieves covalent bonding to the cell membrane, enabling prolonged retention of the PS on the cell surface and the in situ generation of reactive oxygen species (ROS) on cell membranes to kill tumor cells. In vivo studies demonstrated a 3.3-fold increase in tumor accumulation of the PS through bioorthogonal reactions compared to the control group, confirming that click chemistry can effectively enhance PS tumor accumulation. This approach allows for the effective elimination of tumors with a single treatment. The improved efficiency of this strategy provides new insights into the design of PDT systems for potential clinical applications.

Photodynamic and photothermal bacteria targeting nanosystems for synergistically combating bacteria and biofilms

The escalating hazards posed by bacterial infections underscore the imperative for pioneering advancements in next-generation antibacterial modalities and treatments. Present therapeutic methodologies are frequently impeded by the constraints of insufficient biofilm infiltration and the absence of precision in pathogen-specific targeting. In this current study, we have used chlorin e6 (Ce6), zeolitic imidazolate framework-8 (ZIF-8), polydopamine (PDA), and UBI peptide to formulate an innovative nanosystem meticulously engineered to confront bacterial infections and effectually dismantle biofilm architectures through the concerted mechanism of photodynamic therapy (PDT)/photothermal therapy (PTT) therapies, including in-depth research, especially for oral bacteria and oral biofilm. Ce6@ZIF-8-PDA/UBI nanosystem, with effective adhesion and bacteria-targeting, affords a nuanced bacterial targeting strategy and augments penetration depth into oral biofilm matrices. The Ce6@ZIF-8-PDA/UBI nanosystem potentiated bacterial binding and aggregation. Upon exposure to red-light (RL) irradiation, Ce6@ZIF-8-PDA/UBI showed excellent antibacterial effect on S. aureus, E. coli, F. nucleatum, and P. gingivalis and exceptional light-driven antibiofilm activity to P. gingivalis biofilm, which was a result of the efficient bacterial localization mediated by PDA/UBI, as well as the PDT/PTT facilitated by Ce6/PDA interactions. Collectively, these versatile nanoplatforms augur a promising and strategic avenue for controlling infection and biofilm, thereby holding significant potential for future integration into clinical paradigms. The original application of the developed nanosystem in oral biofilms also provides a new strategy for effective oral infection treatment.

Novel [3+2+1] Coordinated Iridium (III) Complexes for Hyperefficient Photodynamic Therapy

ABSTRACTEfficient photosensitizers are crucial for the success of photodynamic therapy (PDT). Herein, we reported two [3+2+1] coordinated organometallic Iridium (III) complexes (labeled as Ir‐C1 and Ir‐C4). Ir‐C1/C4 can generate both type I and type II reactive oxygen species (ROS). In vitro experiments, Ir‐C1/C4 show low biotoxicity and high phototoxicity of half‐maximal inhibitory concentration values of 14 nM and 33 nM on rectal cancer cell line HCT116, respectively. Western blot analysis revealed that the Ir‐C1/C4 activated ferroptosis, apoptosis, and inhibiting autophagy simultaneously. Proteomics analysis demonstrated that the photosensitizers destroyed the endoplasmic reticulum (ER), blocking the signal transmission and material transfer between the ER and other tissues of the cell, especially the ER to Golgi vesicle‐mediated transport. Ir‐C1/C4 can achieve better antitumor performance than commercial photosensitizer Chlorin e6 and the ferroptosis activator RSL3 at lower concentrations. The low biotoxicity and high phototoxicity make them ideal candidates for PDT. The findings provide new insights into the design of photosensitizers for metal complexes and have significant implications for the development of PDT and related drugs.

A Powerful Organic Photosensitizer for Effective Treatment of Malignant Tumors Via Activating Antitumor Immunity.

Photodynamic therapy (PDT) has emerged as an innovative approach in cancer treatment, effectively inducing tumor cell death through light-triggered reactive oxygen species (ROS) generation. Additionally, PDT can also trigger antitumor immune responses, thereby reducing the risk of postoperative tumor recurrence. However, the development of highly efficient photosensitizers aimed at activating immune responses for comprehensive tumor eradication remains at an early stage. In this study, we developed a new organic photosensitizer, ThC, which exhibits excellent mitochondrial-targeting effect and significantly enhanced ROS production compared to traditional photosensitizers, such as Chlorin e6 (Ce6). Our findings demonstrate that ThC robustly induces immunogenic cell death (ICD) process in hepatic cancer cells, which could effectively transform immunologically "cold" tumors into "hot" tumors. Through in situ injection and subsequent white light irradiation, ThC achieved superior efficacy in eliminating subcutaneous hepatic tumors. Immunological analyses revealed that ThC treatment led to elevated levels of CD4+ and CD8+ T cells, along with a reduction in immunosuppressive cell populations (Tregs and tumor-associated macrophages) within the tumor microenvironment. This study provides a novel therapeutic agent with significant potential for clinical translation for the treatment of malignant tumors.

Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy.

The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration and low drug delivery. In this study, we addressed these challenges by developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced cell and tissue permeability. The CPPD1 molecule, a bioconjugate of a hydrophobic photosensitizer and strongly positively charged programmed cell death-ligand 1 (PD-L1) binding cell-penetrating peptide (CPP), is capable of self-assembling into nanoparticles with an average size of 199 nm in aqueous solution without the need for any carriers. These carrier-free nanoparticles possess the ability to penetrate the cell membrane of cancer cells and target tumors expressing PD-L1 on their surface. Notably, CPPD1 nanoparticles effectively blocked programmed cell death-1 (PD-1)/PD-L1 interactions and reduced PD-L1 expression via lysosomal degradation. They also demonstrated the responsiveness of CPPD1 nanoparticles in photodynamic therapy (PDT) to a 635 nm laser, leading to the generation of ROS, and induction of various immunogenic cell deaths (ICD). Highly penetrating CPPD1 nanoparticles could immunogenically modulate the microenvironment of CT26 cancer and were also effective in treating abscopal metastatic tumors, addressing major limitations of traditional PDT.

Use of UMFNPs/Ce6@MBs in multimodal imaging-guided sono-photodynamic combination therapy for hepatocellular carcinoma.

Early diagnosis of liver cancer and appropriate treatment options are critical for obtaining a good prognosis. However, due to technical limitations, it is difficult to make an early and accurate diagnosis of liver cancer, and the traditional imaging model is relatively simple. Therefore, we synthesized multifunctional diagnostic/therapeutic nanoparticles, UMFNPs/Ce6@MBs, loaded with ultra-small manganese ferrite nanoparticles (UMFNPs) and chlorin e6 (Ce6). This nanoplatform can take full advantage of hypoxia, acidic pH (acidosis) and increased levels of reactive oxygen species (e.g. H2O2) in the tumor microenvironment (TME). Specific imaging and drug release can also enhance tumor therapy by modulating the hypoxic state of the TME to achieve the combined effect of sonodynamic therapy and photodynamic therapy (SPDT). In addition, the prepared UMFNPs/Ce6@MBs have H2O2 and pH-sensitive biodegradability and can release UMFNPs and photosensitizer Ce6 in the TME while producing O2 and Mn2+. The obtained Mn2+ ion nanoparticles can be used for T1 magnetic resonance imaging of tumor-bearing mice, and the released Ce6 can provide fluorescence imaging function at the same time. Because UMFNPs/Ce6@MB ultrasonic microbubbles show good ultrasonic imaging results, UMFNPs/Ce6@MBs can simultaneously provide multi-modal imaging functions for magnetic resonance imaging (MRI), ultrasound and fluorescence imaging. In conclusion, UMFNPs/Ce6@MBs realize the synergistic treatment of SDT and PDT under multi-mode near-infrared fluorescence imaging and CEUS monitoring, demonstrating its great potential in tumor precision medicine.

Photocrosslinking of hyaluronic acid-based hydrogels through biotissue barriers.

Photocrosslinkable hydrogels based on hyaluronic acid are promising biomaterials high in demand in tissue engineering. Typically, hydrogels are photocured under the action of UV or blue light strongly absorbed by biotissues, which limits prototyping under living organism conditions. To overcome this limitation, we propose the derivatives of well-known photosensitizers, namely chlorin p6, chlorin e6 and phthalocyanine, as those for radical polymerization in the transparency window of biotissues. Taking into account the efficiency of radical generation and dark and light cell toxicity, we evaluated water miscible pyridine phthalocyanine as a promising initiator for the intravital hydrogel photoprinting of hyaluronic acid glycidyl methacrylate (HAGM) under irradiation near 670 nm. Coinitiators (dithiothreitol or 2-mercaptoethanol) reduce the irradiation dose required for HAGM crosslinking from ∼405 J cm-2 to 80 J cm-2. Patterning by direct laser writing using a scanning 675 nm laser beam was performed to demonstrate the formation of complex shape structures. Young's moduli typical of soft tissue (∼270-460 kPa) were achieved for crosslinked hydrogels. The viability of human keratinocytes HaCaT cells within the photocrosslinking process was shown. To demonstrate scaffolding across the biotissue barrier, the subcutaneously injected photocomposition was crosslinked in BALB/c mice. The safety of the irradiation dose of 660-675 nm light (100 mW cm-2, 15 min) and the non-toxicity of the hydrogel components were confirmed by histomorphologic analysis. The intravitally photocrosslinked scaffolds maintained their shape and size for at least one month, accompanied by slow biodegradation. We conclude that the proposed technology provides a lucrative opportunity for minimally invasive scaffold formation through biotissue barriers.

Self-assembly nanomedicine initiating cancer-immunity cycle with cascade reactions for boosted immunotherapy

Immune checkpoint blockade (ICB) therapy has been extensively integrated into cancer clinical management. However, its overall response rate is limited due to the stagnating cancer-immunity cycle (CIC) caused by the immunosuppressive tumor microenvironment (TME). Here, a multi-pronged nanomedicine, defined as LCCS, was constructed by the self-assembly of lactate oxidase, catalase, chlorin e6, and sorafenib. Through cascade reactions, LCCS effectively reprogrammed the TME and re-initiated the CIC by depleting lactate, alleviating hypoxia, inducing immunogenic cell death, and normalizing tumor vessels. Immunological analyses indicated that treatment with LCCS decreased the infiltration of immunosuppressive cells while increasing the recruitment of immune effector cells in tumors. Leveraging the effective operation of the CIC, LCCS improved the efficacy of ICB therapy to inhibit breast cancer, and effectively induced the elimination of colorectal cancer and long-term immune memory. Therefore, multifunctional nanomedicines targeting CIC hold great potential for applications in cancer immunotherapy.

Macrophage membrane-camouflaged pure-drug nanomedicine for synergistic chemo- and interstitial photodynamic therapy against glioblastoma.

Glioblastoma (GBM) persists as a highly fatal malignancy, with current clinical treatments showing minimal progress over years. Interstitial photodynamic therapy (iPDT) holds promise due to its minimally invasive nature and low toxicity but is impeded by poor photosensitizer penetration and inadequate GBM targeting. Here, we developed a biomimetic pure-drug nanomedicine (MM@CT), which co-assembles the photosensitizer chlorin e6 (Ce6) and the first-line chemotherapeutic drug (temozolomide, TMZ) for GBM, then camouflaged with macrophage membranes. This design eliminates the need for traditional excipients, ensuring formulation safety and achieving exceptionally high drug loading with 73.2 %. By leveraging the biomimetic properties of macrophage membranes, MM@CT evades clearance by the mononuclear phagocyte system and can overcome blood circulatory barriers to target intracranial GBM tumors due to its inherent tumor-homing ability. Consequently, this targeted strategy enables precise delivery of TMZ to the tumor site while significantly enhancing Ce6 accumulation within the tumor tissue. Upon intra-tumoral irradiation using an optical fiber, activated Ce6 synergizes with TMZ to exert both cytotoxic effects from chemotherapy and unique advantages from iPDT simultaneously attacking GBM tumors in a dual manner. In subcutaneous and intracranial GBM mouse models, MM@CT exhibits remarkable anti-tumor efficacy with minimal systemic toxicity, emerging as a promising GBM treatment strategy. STATEMENT OF SIGNIFICANCE: Glioblastoma (GBM) remains a formidable brain cancer, posing significant therapeutic challenges due to the presence of the blood-brain barrier (BBB) and tumor heterogeneity. To overcome these obstacles, we have developed MM@CT, a biomimetic nanomedicine with exceptional drug loading efficiency of 73.2 %. MM@CT incorporates the photosensitizer Ce6 and chemotherapy agent TMZ, encapsulated within nanoparticles and camouflaged with macrophage membranes. This innovative design enables efficient BBB penetration, precise tumor targeting, and synergistic application of chemotherapy and photodynamic therapy. Encouragingly, preclinical evaluations have demonstrated substantial antitumor activity with minimal systemic toxicity, positioning MM@CT as a promising therapeutic strategy for GBM.

A Chlorin e6 derivative-mediated photodynamic therapy versus doxycycline for moderate-to-severe rosacea: A prospective, randomized, controlled study.

Photodynamic therapy (PDT) is beneficial for managing rosacea, and chlorin e6 derivative-mediated photodynamic therapy (STBF-PDT) has demonstrated efficacy in reducing acne lesions with mild adverse reactions. This study aimed to assess the effectiveness and safety of STBF-PDT for the treatment of moderate-to-severe rosacea. In this prospective, randomised, evaluator-blind controlled study, patients with moderate-to-severe rosacea were assigned to receive up to six STBF-PDT sessions or 100 mg of doxycycline daily for eight weeks, followed by a 24-week follow-up. A total of 76 patients were enrolled (38 assigned to STBF-PDT and 38 to oral doxycycline) with 69 (36 in the STBF-PDT group and 33 in the doxycycline group) completing the study. At the end of treatment, the median reduction in lesion count was 82.3 % in the STBF-PDT group and 81.8 % in the doxycycline group, indicating no significant difference between the groups. The STBF-PDT group exhibited a lower relapse rate and a significantly higher reduction in Demodex mites. Clinician's Erythema Assessment success (CEA), sensations of burning and pruritus, telangiectasia, and Rosacea-related Quality of Life (RosaQoL) scores were comparable between groups. No severe adverse reactions were observed. STBF-PDT is a promising treatment option for mild-to-moderate rosacea with mild adverse reactions.

Octreotide modified self-assembly Chlorin e6 nanoparticles with redox responsivity and active targeting for highly selective pancreatic neuroendocrine neoplasms photodynamic therapy

Pancreatic neuroendocrine neoplasms (pNENs) are characterized by high rarity and heterogeneity, simultaneously suffering from a lack of the satisfactory treatment options with high pNENs-selectivity and safety. Therefore, it is urgent for us to develop a novel drug delivery system and/or explore new treatment strategies. Photodynamic therapy (PDT) is a clinically used tumor treatment modality, which yet has not been reported in pNENs. Herein, we designed a redox tumor microenvironment-activatable self-assembly Chlorin e6 (Ce6) nanoparticles (OCNPs) containing the somatostatin receptor (SSTR)-targeted octreotide (OCT), and conducted in vivo and in vitro evaluations on its role in PDT for pNENs. OCNPs exhibited and excellent stability and sensitivity to GSH/ROS to release Ce6 which produced a large amount of 1O2 under laser irradiation. In addition, OCNPs could specifically recognize the SSTR on the surface of pNENs cells through OCT and enter the cells by receptor-mediated endocytosis, highlighting a good active targeting ability. The mechanism research elucidated that OCNPs had a significant phototoxic effect (IC50 = 1.174 uM) on pNENs cells mainly by blocking cells in G0/G1 phase, and increasing cell apoptosis and necrosis. Importantly, the in vivo experiment proved that OCNPs enable selective and prolonged tumor accumulation, thus leading to a better therapeutic efficacy compared with Ce6, with no obvious toxic and side effects on major organs. Our research is the first case that employed PDT for pNENs, and these positive results demonstrated the pNENs-targeted Ce6 delivery system is promising to advance the treatment of pNENs.

ВОДОРАСТВОРИМЫЙ ПРЕПАРАТ НА ОСНОВЕ ХЛОРИНА Е6 С ЦИТРАТОМ ЕВРОПИЯ КАК ПОТЕНЦИАЛЬНЫЙ ФОТОСЕНСИБИЛИЗАТОР НОВОГО ПОКОЛЕНИЯ

The present study is directed towards synthesis a water-soluble substance for photodynamic therapy. It is an aqueous solution containing Chlorin e6 as a photosensitizer and europium citrate as a scintillator. The ionic composition of the solution was determined using ESI mass spectrometry. The conclusion was made about the nonradiative energy transfer from europium to Chlorin e6 with subsequent luminescence of the latter based on the analysis of the luminescence spectrum of the solution containing the conjugate [Eu:H2Cit:Chlorin e6=1:1:1]2-We studied dark toxicity «in vitro». It was shown that in the range of introduced PS concentrations from 3.13 to 100 μg/ml, the percentage of viable cells varied from 91.64±4.58% to 24.14±1.21%, which confirms the prospect of further study of the new substance